Hemolytic Anemias Quiz

Pathophysiology PHMU 534, Lecture 10: RBC Disorders I

• Course title: Pathophysiology PHMU 534
• Lecture: 10
• Topic: Red Blood Cell (RBC) Disorders
• Lecturer: Dr. Radwa Sabry

Competencies

• Domain 1: Fundamental Knowledge
  • Demonstrate understanding of pathophysiological mechanisms of diseases.
  • Use correct medical terminology in pharmacy practice.
  • Relate disease mechanisms to clinical manifestations and possible complications.
  • Utilize scientific literature and interpret information for professional decision-making.
• Domain 2: Professional and Ethical Practice
  • Recognize physician roles in the healthcare team and perform responsibilities in compliance with professional structure.
• Domain 3: Pharmaceutical Care
  • Apply body function principles and genomics to manage diseases.
  • Relate etiology, epidemiology, pathophysiology, diagnosis and clinical features to guide pharmacotherapeutic approaches.
• Domain 4: Personal Practice
  • Demonstrate responsibility for team performance and provide peer evaluation, expressing time management skills.
  • Independently retrieve and critically analyze information, and work effectively within a team.
  • Demonstrate effective communication (verbal, non-verbal, and written) within the professional healthcare team, patients, and communities.
  • Utilize contemporary technologies and media to present effectively.
  • Engage in independent learning for continuous professional development.

Outline

• Overview of Anemia
  • Blood loss anemia (hemorrhage)
  • Hemolytic anemias
    • Hereditary spherocytosis
    • Sickle cell anemia
    • Thalassemia
    • Glucose-6-phosphate dehydrogenase deficiency
    • Immunohemolytic anemia
  • Anemia of diminished erythropoiesis
    • Iron deficiency anemia
    • Aplastic anemia

Causes of Anemia

• Increased RBC destruction (Hemolytic Anemia)
  • Intrinsic (Intracorpuscular)
  • Extrinsic (Extracorpuscular)
• Decreased RBC production
  • Inadequate supply (Iron deficiency)
  • Disturbed proliferation and maturation of erythroblasts
  • Marrow replacement and infiltration
• Bleeding
  • Chronic (e.g., GI lesions, gynecological disturbances)

RBC Reference Ranges

• Hemoglobin (Hb): (g/dL) Men: 13.2-16.7, Women: 11.9-15.0
• Hematocrit (Hct): (%) Men: 38-48, Women: 35-44
• Red blood cell count: (x10⁶/μL) Men: 4.2-5.6, Women: 3.8-5.0
• Other relevant values(MCV, MCH, MCHC, RDW) are also included.

Morphology

• Normal erythrocyte: Size 6-9µm, MCV 80-97fL
• Microcytic hypochromic: Size <6µm, MCV <80fL
• Normocytic normochromic: Size 6-9µm, MCV 80-97fL
• Macrocytic: Size >9µm, MCV >100fL

Anemia of Blood Loss

• Acute blood loss
  • If >20% blood volume lost, immediate threat is hypovolemic shock, not anemia
  • RBCs are normocytic and normochromic
  • Erythropoietin level rises
• Chronic blood loss
  • Iron stores gradually depleted
  • Iron deficiency anemia
  • Microcytic and hypochromic anemia

Hemolytic Anemias

• Intrinsic abnormalities (intracorpuscular)
  • Membrane skeleton proteins (e.g., hereditary spherocytosis)
  • Enzyme deficiency (e.g., G6PD deficiency)
• Extrinsic abnormalities (extracorpuscular)
  • Abnormal globin synthesis (e.g., sickle cell anemia, thalassemias)
  • Antibody mediated (e.g., immune hemolytic anemia)

Features of Hemolytic Anemias

• Decreased RBC lifespan, leading to premature destruction
• Erythroid hyperplasia in the bone marrow (compensation)
• Reticulocytosis
• Extramedullary hematopoiesis in severe cases (liver, spleen, lymph nodes)

RBC Hemolysis

• Intravascular hemolysis
  • Mechanical forces (e.g., defective heart valve)
  • Biochemical (e.g., exposure to toxins)
  • Jaundice, hyperbilirubinemia (unconjugated), haptoglobin decrease, hemosiderinuria, hemoglobinemia, hemoglobinuria, LDH increase.
• Extravascular hemolysis
  • Reduction in RBC deformability
  • Jaundice, hyperbilirubinemia (unconjugated), haptoglobin decrease (if severe), bilirubin-rich gallstones, no hemoglobinemia, no hemoglobinuria, splenomegaly

Hereditary Spherocytosis

• Pathogenesis: Mutations in membrane proteins (ankyrin, band 3, spectrin) reduce membrane stability
• Morphology: Spherocytes (lack central pallor)
• Clinical features: Moderate anemia, jaundice, splenomegaly, aplastic crises (parvovirus B19), increased osmotic fragility.
• Treatment: Splenectomy (balancing the risk of infection). Partial splenectomy is increasingly common, as it can improve outcomes, while protecting against sepsis.

Sickle Cell Anemia

• Pathogenesis: Point mutation in β-globin gene (Glu → Val) leads to abnormal hemoglobin (HbS), polymer formation and sickling under deoxygenation
• Consequences: Hemolysis, vaso-occlusion, pain crises, organ damage. Microvascular obstructions
• Morphology: Sickled cells (elongated crescentic or sickle-shaped)
• Clinical features: Chronic hemolytic anemia, episodic pain crises, acute chest syndrome, stroke, splenic sequestration, (autosplenectomy likely by adulthood), aplastic crises (parvovirus B19), infections,
• Factors affecting sickling: intracellular concentration of HbS, presence of other hemoglobins (HbF, HbA2) and co-existence of α-thalassemia which reduces sickling.
• Epidemiology: Common in malaria-endemic regions due to protective effect; also present in other populations. High frequency in specific geographic areas.

Sickle cell anemia factors affecting sickling:

• The presence of other hemoglobin (HbF, HbA2)
• Intracellular concentration of HbS
• The transit time for RBCs through the microvasculature (slow blood flow)

Other Topics (from the slides)

• Epidemiology, normal hemoglobin, references are also included in detailed notes

• Clinical features of both conditions are covered.